Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients
Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients
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DOI：
10.1016/s0360-3016(02)02764-5
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发表时间：
2002-07-01
影响因子：
7
通讯作者：
Cosimelli, M
中科院分区：
文献类型：
--
作者：
Valentini, V;Coco, C;Cosimelli, M
目的：评价肿瘤缓解、肿瘤和淋巴结降级以及cTNM、yTNM的影响（放化疗后的临床分期，基于术前影像学），和pTNM分类对直肠癌患者的长期预后的影响，这些患者接受术前5-氟尿嘧啶（5-FU）为基础的同步放化疗。1990年1月至1998年3月，连续165例局部晚期腹膜外直肠癌患者接受术前放化疗。4例患者有cT 2病变（2.5%），120例患者有cT 3病变（74.5%），41例患者有cT 4病变（23%）。在联合成像中，淋巴结受累为cN 0（21%）、cN 1（41%）、cN2（34%）和cN 3（4%）。术前放化疗按I/3方案进行：（1）FUMIR-T3（1990年至1995年）针对cT 3 N 0 -2或cT 2 N1 -2直肠癌患者（82例患者）：37.8戈伊（1.8戈伊/次）加5-Flu，1 g/m2/d，第1-4天，持续输注，丝裂霉素C，10 mg/m2/d，第1天;（2）FUMIR-T4（1990 - 1999年）cT 4 N 0 -3或cT 3 - 4 N3直肠癌患者（40例患者）：45戈伊（1.8戈伊/次）加5-Flu，1 g/m2/d，第1-4天和第29-32天，持续输注，丝裂霉素C，10 mg/m2/d，第1天和第29天;（3）PLAFUR-4（1995 - 1998年）用于cT 3 N 0 -2或cT 2 N1 -2直肠癌患者（42例患者）：50.4戈伊（1.8戈伊/次）+5-FU，1 g/m2/d，第1-4天和第29-32天，持续输注，顺铂，60 mg/m2/d，第1天和第29天。放化疗后4 - 5周，通过影像学研究（CT扫描、经直肠超声检查、钡灌肠、肝脏超声检查、胸部X线检查）和再分期（yTNM）重新评估患者的临床反应。在放化疗后6-8周进行手术。FUMIR-T4方案组26例患者接受辅助化疗（5-FU + 1-亚叶酸）。根据临床反应和cTNM、yTNM和pTNM分类评价局部控制（LC）、无远处转移（FDM）、无病生存期和总生存期（OS）。结果：cT 2、cT 3和cT 4的5年生存率分别为100%、77%和62%（p = 0.0497）;放化疗后，pT 0-pT 2的5年生存率在81%和91%之间，pT 3和pT 4的5年生存率分别降至66%和47%（p = 0.014）。在第一阶段，cT 3的5年局部控制率为84%，cT 4为72%;放化疗后，pT阶段与LC显著相关（p = 0.0012）：pT 0为100%，pT 1为83%，pT 2为88%，pT 3为79%，pT 4为46%。N分期在预测FDM和OS方面具有统计学意义。还记录了肿瘤缓解、肿瘤降级和淋巴结降级对LC、FDM、无病生存期和OS的显著影响。如果残留肿瘤在手术前有肿瘤指数
Purpose: To evaluate the impact of tumor response; tumor and nodal downstaging; and cTNM, yTNM (clinical stage after chemoradiation, based on preoperative imaging), and pTNM classifications on long-term outcome in patients with rectal cancer treated with preoperative 5-fluorouracil (5-FU)-based concurrent chemoradiation.Methods and Materials: Between January 1990 and March 1998, 165 consecutive patients with locally advanced extraperitoneal cancer of the rectum were treated with preoperative chemoradiation. Four patients had a cT2 lesion (2.5%), 120 had a cT3 lesion (74.5%), and 41 had a cT4 lesion (23%). The nodal involvement at combined imaging was cN0 in 21%, cN1 in 41%, cN2 in 34%, and cN3 in 4%. Preoperative chemoradiation was delivered according to I of 3 schedules: (1) FUMIR-T3 (from 1990 to 1995) for patients with cT3N0-2 or cT2N1-2 rectal carcinoma (82 patients): 37.8 Gy (1.8 Gy/fraction) plus 5-Flu, 1 g/m(2)/d on Days 1-4, continuous infusion, and mitomycin-C, 10 mg/m(2)/d on Day 1; (2) FUMIR-T4 (from 1990 to 1999) for patients with cT4N0-3 or cT3-4N3 rectal carcinoma (40 patients): 45 Gy (1.8 Gy/fraction) plus 5-Flu, 1 g/m(2)/d on Days 1-4 and 29-32, continuous infusion, and mitomycin-C, 10 mg/m(2)/d on Days 1 and 29; and (3) PLAFUR-4 (from 1995 to 1998) for patients with cT3N0-2 or cT2N1-2 rectal carcinoma (42 patients): 50.4 Gy (1.8 Gy/fraction) plus 5-FU, 1 g/m(2)/d on Days 1-4 and 29-32, continuous infusion, and cisplatin, 60 mg/m(2)/d on Days 1 and 29. Four to five weeks after chemoradiation, patients were reevaluated for clinical response by imaging studies (CT scan, transrectal ultrasonography, barium enema, liver ultrasonography, chest X-rays) and restaged (yTNM). Surgery was performed 6-8 weeks after chemoradiation. Adjuvant chemotherapy (5-FU + 1-folinic acid) was delivered to 26 patients in the FUMIR-T4 protocol group. Local control (LC), freedom from distant metastases (FDM), disease-free survival, and overall survival (OS) were evaluated according to the clinical response and cTNM, yTNM, and pTNM classification. The median follow-up was 67 months.Results: The 5-year survival rate was 100% for cT2, 77% for cT3, and 62% for cT4 (p = 0.0497); after chemoradiation, it ranged between 81% and 91% for pT0-pT2 and dropped to 66% for pT3 and 47% for pT4 (p = 0.014). The 5-year local control rate was, at the first staging, 84% for cT3 and 72% for cT4; after chemoradiation, the pT stage correlated significantly with LC (p = 0.0012): 100% for pT0, 83% for pT1, 88% for pT2, 79% for pT3, and 46% for pT4. N stage was statistically significant in predicting FDM and OS at any staging step. A significant impact of tumor response, tumor downstaging, and nodal downstaging on LC, FDM, disease-free survival, and OS was also recorded. If the residual tumor, before surgery, had a tumor index